A Phase IIa, Single-arm, Multicenter Study to Investigate the Clinical Activity and Safety of Avelumab in Combination With Cetuximab Plus Gemcitabine and Cisplatin in Participants With Advanced Squamous NSCLC
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 20
- 主要终点
- Percentage of Participants With Confirmed Best Objective Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Assessed by Investigator
研究概览
简要总结
The main purpose of the study was to investigate the clinical activity and safety of avelumab in combination with cetuximab plus gemcitabine and cisplatin in participants with treatment-naïve advanced squamous non-small-cell lung cancer (NSCLC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically-confirmed Stage IV metastatic or recurrent (Stage IV) NSCLC of squamous histology
- •Availability of formalin-fixed paraffin-embedded (FFPE) block containing tumor tissue or a minimum of 15 (preferably 25) unstained tumor slides (cut within 1 week) suitable for Programmed death ligand 1 (PD-L1) expression and epidermal growth factor receptor (EGFR) expression/amplification assessments
- •At least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) v1.1 criteria
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at study entry
- •Adequate hematological, hepatic and renal function
- •Estimated life expectancy of at least 3 months
- •Can give signed informed consent
- •Other protocol defined inclusion criteria could apply
排除标准
- •Participants whose tumor disease harbors an activating EGFR mutation or ALK rearrangement. Participants with tumors of unknown EGFR or ALK status will require testing only in never smokers
- •All participants with brain metastases with protocol defined exceptions
- •Previous malignant disease (other than NSCLC) within the last 5 years (except adequately treated non-melanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate) unless a complete remission without further recurrence was achieved at least 2 years prior to study entry and the participant was deemed to have been cured with no additional therapy required or anticipated to be required
- •Active infection requiring systemic therapy
- •Known history of human immunodeficiency virus or known acquired immunodeficiency syndrome
- •Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV ribonucleic acid (RNA) if anti-HCV antibody screening test positive)
- •Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
- •Interstitial parenchymal lung disease
- •Pregnancy or lactation
- •Known alcohol or drug abuse as determined by the Investigator
- •History of uncontrolled intercurrent illness
- •Clinically significant (that is active) cardiovascular disease
- •Known history of inflammatory colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis
- •Any psychiatric condition that would prohibit the understanding or rendering of informed consent or that would limit compliance with study requirements
- •Prior/Concomitant Therapy as described in protocol
- •Use of any investigational drug within 28 days before the start of study treatment
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Avelumab and Cetuximab
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
干预措施: Avelumab (Drug)
Avelumab and Cetuximab
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
干预措施: Cetuximab (Drug)
Avelumab and Cetuximab
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
干预措施: Gemcitabine (Drug)
Avelumab and Cetuximab
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
干预措施: Cisplatin (Drug)
Avelumab and Cetuximab
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Percentage of Participants With Confirmed Best Objective Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Assessed by Investigator
时间窗: Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 612 days)
Confirmed BOR was defined as the percentage of participants who achieved confirmed complete responses (CR) or partial response (PR), according to RECIST version 1.1 assessed by the Investigator.CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Confirmed CR=as at least two determinations of CR at least 4 weeks apart with no PD. Confirmed PR=as at least 2 determinations of PR or better (PR followed by PR or PR followed by CR), at least 4 weeks apart (not qualifying for a CR) with no PD in between. Percentage of Participants with confirmed BOR were reported.
次要结局
- Duration of Response (DOR)(Time from the first dose of study drug until occurrence of PD, death due to any cause or last tumor assessment (assessed up to 612 days))
- Progression-Free Survival (PFS) Time Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 737 days))
- Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab(Pre-dose, 2 hours after end of infusion on Day 1, 8, 22 and 29; Pre-dose, 30 minutes after the end of infusion on Day 43, 50, 64, 71; Pre-dose, 3 hours after end of infusion on Day 85, 99, 113, 127, 169, 253, and 337)
- Serum Trough Concentration Levels (Ctrough) of Avelumab(Pre-dose: Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 99, Day 113, Day 127, Day 169, Day 253 and Day 337)
- Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab(Pre-dose, 2 hours after end of infusion on Day 1, 8, 22 and 29; Pre-dose, 30 minutes after the end of infusion on Day 43, 50, 64, 71; Pre-dose, 3 hours after end of infusion on Day 85, 99, 113, 127, 169, 253, and 337)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (AEs), Treatment-Related Grade >=3 TEAEs and Immune-related Treatment Emergent AEs (irTEAEs)(Time from the first dose of study drug assessed up to (941 days))
- Number of Participants With Positive Anti-Drug Antibody (ADA) of Avelumab(Pre-dose up to 149 days)
- Serum Trough Concentration Levels (Ctrough) of Cetuximab(Pre-dose: Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 99, Day 113, Day 127, Day 169, Day 253 and Day 337)
- Overall Survival (OS)(Time from the first dose of study drug until occurrence of death due to any cause (assessed up to 941 days))
- Number of Participants With Positive Anti-Drug Antibody (ADA) of Cetuximab(Pre-dose up to 149 days)